Reduction of infections in healthcare settings using photocatalytic compositions

ABSTRACT

Methods of reducing the incidence of healthcare-associated infections in various healthcare settings are provided. Methods for preventing or reducing the number of infections in a human or animal population are also provided. The methods as provided herein reduce the presence of various infectious agents that are commonly acquired or transmitted and are present on both animate and inanimate surfaces, including those infectious agents commonly found in healthcare settings. By reducing the presence of such infectious agents, the incidence of various types of infection or disease is thereby reduced.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/015,596 filed Jun. 23, 2014, the content of which is incorporatedherein in its entirety.

FIELD

The present disclosure relates to preventing and reducing the incidenceof infectious agents found on a surface and particularly on surfacesfound in healthcare settings.

BACKGROUND

Infectious agents found in and on building structures and surfaces ofobjects therein can lead to various health problems. Common offendinginfectious agents include microorganisms such as bacteria (e.g., gramnegative rods such as Escherichia coli and gram-positive cocci such asStaphylococcus aureus). These and other bacteria can cause healthproblems such as dermal infections, respiratory infections, intestinalinfections, and kidney disease. Also, pathogenic viruses such asinfluenza viruses are commonly found in buildings where they spreadamong those occupying the structure. Particularly, infectious agentswithin healthcare settings lead to healthcare-associated infectionswhich, in turn, result in greater than a billion dollars in excesshealthcare costs annually. These infections have created a challenge forhealthcare management teams due to multi-drug resistant bacteriabecoming commonplace in healthcare settings such as hospices, hospitals,and assisted-living or long-term care facilities.

Systems and methods designed to encourage, effect, monitor and enforcehand sanitation and other hygienic practices may aid in the reduction ofthe spread of infectious agents in healthcare settings, however, suchmeasures alone are not sufficient. Thus, there remains a need forcompositions and associated methods that prevent and reduce the presenceof infectious agents in a variety of settings, including healthcaresettings or facilities.

SUMMARY

According to one aspect, a method of reducing the incidence ofhealthcare-associated infections in a healthcare facility is provided.The method includes the step of treating at least one inanimate surfaceof the healthcare facility structure, or at least one object therein, ora combination thereof, with a photocatalytic composition. Thephotocatalytic composition comprises, consists essentially of, orconsists of titanium dioxide (TiO₂) doped with zinc and at least oneother doping agent.

According to one embodiment, the healthcare-associated infectionssusceptible to treatment include bone infection, joint infection,bloodstream infection, central nervous system infection, cardiovascularsystem infection, pneumonia, reproductive tract infection, and surgicalsite infection. According to another embodiment, thehealthcare-associated infections susceptible to treatment includegastrointestinal infection, lower respiratory infection, upperrespiratory infection, skin or soft tissue infection, bloodstreaminfection, eye infection, ear infection, nose infection, throatinfection, mouth infection, and urinary tract infection.

The method is suitable for reducing the abundance in air and on surfacesof infectious agents including, but not limited to species ofAcinetobacter, adenovirus, Bacillus, Burkholderia, Bordetella, Brucella,caliciviruses, herpes including zoster (chickenpox), Clostridium, coronaviruses including SARS, MERS, and PEDV, Enterococcus, Escherichia,Hemophilus, hepatitis viruses A and B, influenza and parainfluenzaviruses, Klebsiella, Listeria, Legionella, measles virus, mumps virus,Mycobacterium, Neisseria, norovirus, Pseudomonas, parvovirus,poliovirus, rhinovirus, respiratory syncytial virus, rotavirus, rubella,Salmonella, Streptococcus, Staphylococcus, and Vibrio. The infectiousagents that are reduced include both those susceptible to antibioticsand, without limitation, those resistant to antibiotics such as MRSA(methicillin-resistant Staphylococcus aureus, VISA (vancomycinintermediate Staphylococcus aureus), MRE (multiply resistantenterococci), and VRE (vancomycin-resistant enterococci).

According to one embodiment, the photocatalytic composition is appliedat a rate of from about 500 ft² per liter to about 1800 ft² per liter.According to one embodiment, the photocatalytic composition is appliedby spraying, atomizing, coating, immersion, or dipping.

According to one embodiment, the incidence of healthcare-associatedinfections is reduced by at least 20% over a twelve month period afterone treatment. According to another embodiment, the incidence ofhealthcare-associated infections is reduced by at least 30% over atwelve month period after one treatment.

According to one embodiment, the at least one inanimate surface of thehealthcare facility structure includes any or all walls, fixtures,floors, and ceilings, including those parts of hallways, offices,bathrooms, elevators, stairwells, and kitchens/cafeterias, common areas,nurses' stations, and doctors' stations. According to one embodiment,the at least one object of the healthcare facility includes thecurtains, call buttons, computers, monitors, wall computer kiosks, bloodpressure cuffs, wheelchairs, lifts, carts, and beds.

According to one embodiment, the photocatalytic composition utilized inthe methods provided herein comprises, consists essentially of, orconsists of titanium dioxide that is doped with zinc and at least oneother doping agent. According to one embodiment, the doping agent(s)increase the absorbance of light across the range of about 200 nm toabout 500 nm. According to one embodiment, the absorbance of light ofwavelengths longer than about 450 nm is less than 50% the absorbance oflight of wavelengths shorter than about 350. According to oneembodiment, the at least one other doping agent (i.e., in addition tozinc) can be one or more of Ag, Si, C, S, Fe, Mo, Ru, Cu, Os, Re, Rh,Sn, Pt, Li, Na, and K. According to one embodiment, the titanium dioxidenanoparticles have an average particle size of from about 2 nm to about20 nm. According to one embodiment, the at least one other doping agentis silicon. According to one embodiment, the at least one other dopingagent is silicon dioxide. According to one such embodiment, thephotocatalytic composition exhibits a ratio of titanium dioxide tosilicon dioxide of from about 3 to about 20. According to yet anotherembodiment, the photocatalytic composition exhibits a ratio of titaniumdioxide to zinc from about 5 to about 150 and a ratio of titaniumdioxide to silicon dioxide from about 1 to about 500. According to oneembodiment, the photocatalytic composition comprises, consistsessentially of, or consists of (A) about 5000 to about 10000 ppm oftitanium dioxide, (B) about 50 to about 150 ppm of zinc, and (C) about300 to about 1000 ppm of silicon dioxide.

According to another aspect, a method for preventing or reducing thenumber of infections in a human or animal population is provided. Themethod includes the step of treating inanimate surfaces of a structureoccupied by the population, or at least one inanimate object presenttherein, or a combination thereof, with a photocatalytic composition.The photocatalytic composition comprises, consists essentially of, orconsists of titanium dioxide doped with zinc and at least one otherdoping agent. According to one embodiment, the structure occupied by thepopulation includes an agricultural facility, food-processing facility,catering facility, restaurants, hotel, motel, office, or childcarefacility.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphic representation of solar energy capture of variousTiO₂ compositions.

FIG. 2 is a graphic representation of the photocatalytic activity ofvarious TiO₂ compositions when irradiated at 354 nm.

DETAILED DESCRIPTION

Methods of reducing the incidence of healthcare-associated infections invarious healthcare settings are provided. Methods for preventing orreducing the number of infections in a human or animal population arealso provided. The methods as provided herein reduce the abundance ofvarious infectious agents that are commonly acquired or transmitted andare present on both animate and inanimate surfaces, including thoseinfectious agents commonly found in healthcare settings. Further,airborne infectious agents also are reduced because such agents makecontact with treated surfaces and are inactivated. By preventing andreducing the presence of such infectious agents, the incidence ofvarious types of infection or disease is thereby reduced.

As used herein, the phrase, “at least one” means one or more and thusincludes individual components as well as mixtures/combinations.

The term “comprising” (and its grammatical variations) as used herein isused in the inclusive sense of “having” or “including” and not in theexclusive sense of “consisting only of.”

The terms “a” and “the” as used herein are understood to encompass theplural as well as the singular. The terms “doped” or “doping” as usedherein are understood to encompass the introduction of one or moreimpurities (e.g., dopant, doping agent) into a material for the purposeof modifying the properties of the material.

The terms “treatment” and “treating” include mitigation of apre-existing microbial disease or infestation by application orintroduction of a photocatalytic composition as provided herein to aninanimate structure or object or an animate surface.

The terms “prevention” and “prophylaxis” include reduction of theincidence or severity of disease or infestation in either individuals orpopulations.

The term “healthcare-associated infection” as used herein refers to anylocalized or systemic condition resulting from an adverse reaction tothe presence of an infectious agent (or its toxin) that was not presentand without evidence of incubation at the time of admission to ahealthcare setting.

The term “infectious agent” includes, but is not limited to, viruses,mold, and bacteria that cause or contribute to infection or disease inthe human population Such organisms include but are not limited tospecies of Acinetobacter, adenovirus, Bacillus, Burkholderia,Bordetella, Brucella, caliciviruses, herpes including zoster(chickenpox), Clostridium, corona viruses including SARS, MERS, andPEDV, Enterococcus, Escherichia, Hemophilus, hepatitis viruses A and B,influenza and parainfluenza viruses, Klebsiella, Listeria, Legionella,measles virus, mumps virus, Mycobacterium, Neisseria, norovirus,Pseudomonas, parvovirus, poliovirus, rhinovirus, respiratory syncytialvirus, rotavirus, rubella, Salmonella, Streptococcus, Staphylococcus,and Vibrio. The infectious agents that are reduced include both thosesusceptible to antibiotics and, without limitation, those resistant toantibiotics such as MRSA (methicillin-resistant Staphylococcus aureus,VISA (vancomycin intermediate Staphylococcus aureus), MRE (multiplyresistant enterococci), and VRE (vancomycin-resistant enterococci).

Methods of reducing the incidence of healthcare-associated infections invarious healthcare settings as described herein are provided. Accordingto one embodiment, the method includes the step of treating at least oneinanimate surface of the healthcare facility structure, the objects(e.g., medical equipment) therein, or a combination thereof with aphotocatalytic composition as provided herein. Exemplary healthcaresettings that include such structures and objects include, but are notlimited to, hospitals, doctors' offices, elder or specialty care homes(e.g., assisted living, long-term care) and hospices. Exemplarystructures of the facility subject to treatment include, but are notlimited to, the walls, fixtures, floors, and ceilings, including thoseparts of hallways, offices, bathrooms, elevators, stairwells, andkitchens/cafeterias, common areas, nurses' stations, and doctors'stations. Exemplary inanimate objects in such a setting include thevarious equipment or medical devices that may be present including, butnot limited to, curtains, call buttons, computers, monitors, wallcomputer kiosks, blood pressure cuffs, wheelchairs, lifts, carts, beds,and other similar objects.

According to one embodiment, healthcare-associated infections that canbe acquired or transmitted in a healthcare setting and susceptible totreatment with the photocatalytic compositions provided herein include,but are not limited to, bone and joint infection (e.g., osteomyelitis,disc space infection, joint or bursa infection, prosthetic jointinfection), bloodstream infection, central nervous system infection(e.g., intracranial infection, meningitis, or ventriculitis),cardiovascular system infection (e.g., myocarditis, pericarditis,endocarditis, mediastinitis, arterial or venous infection),Eye/ear/nose/throat/mouth infection (e.g., conjunctivitis, earinfection, oral infection, sinusitis, upper respiratory infection,pharyngitis, laryngitis, epiglottitis), gastrointestinal systeminfection (e.g., gastroenteritis, gastrointestinal tract infection,hepatitis, intraabdominal infection, necrotizing enterocolitis), lowerrespiratory infection (e.g., bronchitis, tracheobronchitis, tracheitis),pneumonia, reproductive tract infection (e.g., endometritis, episiotomyinfection, vaginal cuff infection), surgical site infection, skin/softtissue infection (e.g., breast abscess, mastitis, burn infection,circumcision infection, decubitus ulcer infection, infant pustulosis,skin infection, omphalitis), systemic infection, or urinary tractinfection. According to a preferred embodiment, healthcare-associatedinfections that can be acquired or transmitted in a healthcare settingand are usceptible to treatment include gastrointestinal infection,lower respiratory infection, upper respiratory infection, skin or softtissue infection, bloodstream infection, eye infection, ear infection,nose infection, throat infection, mouth infection, and urinary tractinfection.

According to one embodiment, the incidence of healthcare-associatedinfections is reduced by at least 20% over a twelve month period afterone treatment as provided herein. According to a preferred embodiment,the incidence of healthcare-associated infections is reduced by at least30% over a twelve month period after one treatment as provided herein.

The compositions as provided herein may be applied in any known orsuitable manner, including using application techniques such as spraying(e.g., electrostatic), atomizing, coating, immersion, or dipping. Thebest method of application may vary according to the nature of thesurface to be coated. For many settings a preferred method is to useelectrostatic spray, wherein droplets of the aqueous composition rangingin size from 5 micrometers to 100 micrometers are afforded a smallelectrical charge so that the droplets are attracted to the surface tobe coated. In a further preferred technique, the coating is applied as aseries of two to five spraying steps with drying allowed between eachstep. The photocatalytic coating can be applied at a rate of from about500 ft² per liter to about 1500 ft² per liter.

According to yet another embodiment, a method for preventing or reducingthe number of infections in a human or animal population is provided.The method includes treating inanimate structures used by the human oranimal population, the inanimate objects that may be found within suchstructures, or a combination thereof, with a photocatalytic compositionas provided herein. The step of treating the inanimate structures mayinclude treating either a finished structure or a structure underconstruction. Exemplary settings that include such structures andobjects include, but are not limited to, agricultural facilities,food-processing facilities, catering facilities, restaurants, hotels,motels, and childcare facilities. Exemplary parts of the structures thatcan be treated include, but are not limited to, walls, fixtures, floors,and ceilings, including those parts of hallways, offices, bathrooms,elevators, stairwells, and kitchens.

The methods as provided herein utilize photocatalytic compositions thatinclude titanium dioxide (TiO₂) nanoparticles, which are useful in theprevention and reduction of infectious agents found on a surface andparticularly useful in the reduction of healthcare-associatedinfections. The photocatalytic compositions as provided herein,including any nanoparticles therein, are free of any polymer or polymercomposition (e.g., polymer-stabilized inorganic composition). Thephotocatalytic compositions as provided herein can be used to treat bothanimate and inanimate surfaces in a variety of environments where aninfectious agent is located. The photocatalytic compositions providedherein contain only well characterized and safe materials, can be easilyapplied to surfaces using ordinary spray equipment, exhibitphotocatalytic activity, and are effective in settings of low UVirradiance, including interior artificial lighting.

According to one embodiment, the methods as provided herein utilizephotocatalytic compositions that comprise, consist essentially of, orconsist of titanium dioxide (TiO₂) doped with zinc and at least oneother doping agent. Doping agents suitable in the photocatalyticcompositions provided herein, in addition to zinc, include Ag, Si, C, S,Fe, Mo, Ru, Cu, Os, Re, Rh, Sn, Pt, Li, Na, and K, and combinationsthereof. Particularly preferred doping agents include zinc and silicon.

According to one embodiment, the composition comprises, consistsessentially of, or consists of titanium dioxide doped with zinc and theratio of titanium dioxide to zinc is from about 5 to about 150.According to a preferred embodiment, the ratio of titanium dioxide tozinc is from about 40 to about 100. The photocatalytic composition canfurther comprise, consist essentially of, or consist of silicon dioxide(SiO₂). According to such an embodiment, the ratio of titanium dioxideto silicon dioxide can range from about 1 to about 500. According to apreferred embodiment, the ratio of titanium dioxide to silicon dioxideis from about 3 to about 20. According to one embodiment, the titaniumdioxide nanoparticles as provided herein have an average particle sizeof from about 2 nm to about 20 nm.

According to a preferred embodiment, the photocatalytic composition asprovided herein comprises, consists essentially of, or consists of fromabout 5000 to about 10000 ppm of titanium dioxide, from about 50 toabout 150 ppm of zinc, and from about 300 to about 1000 ppm of silicondioxide. According to one embodiment, the photocatalytic composition asprovided herein absorbs electromagnetic radiation in a wavelength rangeof from about 200 nm to about 500 nm. According to one embodiment, theabsorbance of light of wavelengths longer than about 450 nm is less than50% the absorbance of light of wavelengths shorter than about 350 nm.

The invention will be further understood by the following examples,which are intended to be illustrative of the invention, but not limitingthereof.

Example 1

Absorption characteristics of nanoscale TiO₂ were compared to nanoscaleTiO₂ doped with two differing zinc levels and SiO₂, over the wavelengthrange of 350 nm to 500 nm. The nanoparticle compositions weremanufactured by a modified sol-gel process, to produce formulationscontaining nanoparticles of anatase TiO₂ whose average size was 6 to 7nm. Zinc was incorporated as a doping agent to provide either low zinccontent (0.125% relative to TiO₂) or high zinc content (1.25% relativeto TiO₂). When SiO₂ was an additional dopant, it was present at 10%relative to TiO₂. The preparations were dried and absorbance wasmeasured using standard methods for obtaining diffuse reflectancespectra (DRS) of powders. The solar irradiance (hemispherical, 37 degreetilt) from ASTM G173-03 across this spectral range is shown forreference, (See FIG. 1).

It is evident upon inspection that the TiO₂ preparations doped withhetero-atoms absorb more strongly than otherwise similar undoped TiO₂ inthe near-UV and violet region of the spectrum. The doped preparationsabsorb 25 to 35 percent more of the energy available from 400 to 450 nm,a region of the spectrum that is present in typical interior light aswell as sunlight.

Example 2 Photocatalytic Activity of Various Formulations of TiO₂ Dopedwith Zn and SiO₂ Under UV Illumination

The four formulations described in Example 1 were tested for theirphotocatalytic activity in a standardized system. Each preparation wassuspended in water at approximately 8000 ppm and applied to a glasspanel using a robotic high volume low pressure sprayer, and allowed todry for 24 hours. These panels were each attached to a glass tube toform a container, into which was placed 30 ml of an aqueous solution ofmethylene blue at a concentration providing an optical density of 2.3 at664 nm. The tubes were covered with a glass panel and subjected toillumination at an energy density of approximately 0.5 mW/cm² from alamp (GE item F18T8/BLB) affording ultraviolet illumination at 354 nm.This lamp provides no light at wavelengths below 300 nm or above 400 nm.The optical density of the methylene blue solution in each sample wasmonitored over a period of 48 hours and is shown in FIG. 2.

FIG. 2 shows that the nanocoatings caused a decline in optical density,which results from photocatalytic degradation of the organic dyemethylene blue. The coatings that had the higher amounts of dopantsafforded the most rapid declines, consistent with greater absorbance oflight from the lamp in the UV range (354 nm).

Example 3 Photocatalytic Activity of Various Formulations of TiO₂ Dopedwith Zn and SiO₂ Under Visible Light Illumination

The four formulations described in Example 1 were tested for theirphotocatalytic activity in a second system, in which the experimentalillumination was changed to more closely mimic relevant illuminationsuch as daylight or interior light, which are deficient in theultraviolet energy used in Example 2. Also, for this example thenanoparticle formulations were evaluated as colloidal suspensions in 20mM phosphate buffer, pH 7.2, rather than on a static surface. Theexperiment was performed in a 96-well plate format, in which each wellcontained methylene blue (observed OD₆₅₅ ranging from 0.05 to 0.5) and ananoparticle formulation or appropriate controls in a final volume of200 microliters. The plate was illuminated from a distance of 20 cm withlight from two Sylvania Gro-Lux lamps (F20 T12 GRO/AQ). These lamps emitonly 2% of their total emitted energy below 400 nm, whereasapproximately 36% of their total energy is emitted between 380 and 500nm, with a peak at 436 nm (reference: Technical Information Bulletin“Spectral Power Distributions of Sylvania Fluorescent Lamps”, OsramSylvania, www.sylvania.com).

The compositions of the four preparations tested in this experiment wereindependently verified by the analytical technique known as ICP-AES(inductively coupled plasma atomic emission spectrometry), whichdemonstrated their equivalent TiO₂ content and variations in Si and Zncomposition as described in Example 1. The nanoparticle preparationswere diluted in buffer to provide final concentrations of 75 ppm oftitanium dioxide of each formulation, with twenty replicate wells ofeach formulation. After a short period of equilibration in the dark,each plate was exposed to illumination with shaking, and optical densityat 655 nm was measured at multiple times over using a Molecular DevicesSpectraMax Plus spectrophotometer. The observed linear declines inoptical density due to each formulation were measured to give the ratessummarized in Table 1.

TABLE 1 Trial 1 Trial 2 TiO₂, low Zn  0.0017* 0.0016 TiO₂, low Zn, highSi 0.0020 Not tested TiO₂, high Zn, high Si 0.0019 Not tested TiO₂ onlyNot tested 0.0013 *All values reported are the decline in opticaldensity at 655 nm, per minute

It is evident that all the doped TiO₂ formulations show significantlyincreased rates (25% to 50%) compared to the undoped TiO₂ formulation.The magnitude of the increase in the rate of photocatalytic activity ishighly consistent with the increased absorption of light energy in therange of 400 nm to 450 nm that is evident in the spectra described inExample 1.

Example 4

Infections in a long term acute care healthcare facility were evaluatedupon treatment with a photocatalytic composition as provided herein. Theresults show that the typical infections arising in a healthcarefacility may be significantly reduced as a result of such treatment.

A photocatalytic composition including titanium dioxide nanoparticlesdoped with zinc and silicon dioxide was prepared. The individualnanoparticles were approximately six to ten nanometers in dimension, andwere dispersed in water to provide about 8000 ppm TiO₂, about 100 ppmZn, and about 500 ppm SiO₂. This dispersed colloidal suspension of dopednanoparticles was used to coat essentially all accessible surfaces in a42 bed health care facility that provides long term acute care servicesto patients after surgery and other medical procedures.

The coating was applied using the following procedure. Vacant rooms andbathrooms were thoroughly cleaned by housekeeping staff, includingremoval of all linens and surface disinfection according toinstitutional procedures. The photocatalytic coating was then appliedusing electrostatic spray at a rate of about 1200 ft² per liter. Allobjects in the room were coated, including both hard and soft surfacefurniture and nearby walls, window and privacy curtains, and equipmentsuch as call buttons and remote controls. Bathroom walls, fixtures, andfloors were specifically coated. A minimum of 15 minutes was allowed fordrying of coated surfaces, after which the room was ready for occupancy.In addition to patient rooms, all common areas, including hallways,offices, visitor restrooms, elevators, stairwells, kitchen, and nurse'sstations (including computers) were coated. Equipment was also coated,including wall computer kiosks, blood pressure cuffs, wheelchairs,lifts, carts, and other similar surfaces.

The healthcare facility made no changes to institutional infectioncontrol processes or procedures. The number of infections were recordedin compliance with existing institutional protocols. Table 2 reports thenumber of infections occurring in each quarter of the year followingtreatment, compared with the number of infections at the sameinstitution during the same quarter of the year prior to treatment.Infections were fewer in every quarter after treatment than in anyquarter prior to treatment. When summed over the entire assessmentperiod, infections declined 40% in the year following surface coatingwith the photocatalytic composition.

TABLE 2 Infections per three month period Year Before Year After CoatingCoating Q1 17 8 Q2 15 7 Q3 16 11 Q4 12 6

Example 5

The composition described in Example 4 was applied using the proceduredescribed in Example 4 to a 250 bed health care facility that providessub-acute long term residential care. Similar to Example 4, no changewas made to institutional processes or procedures, and infectionsoccurring in the facility were enumerated in accord with standardprotocols. Table 3 reports the number of infections occurring in eachquarter of the year following treatment, compared with the number ofinfections at the same institution during the same quarter of the yearprior to treatment. Infections were fewer in every quarter aftertreatment compared to any quarter prior to treatment. When summed overthe entire assessment period, infections declined 32% in the yearfollowing surface coating with the photocatalytic composition.

TABLE 3 Infections per three month period Year Before Year After CoatingCoating Q1 78 50 Q2 73 52 Q3 58 42 Q4 66 41

The larger size of this facility allowed an examination of selectedcategories of infections, as defined by the USA Centers for DiseaseControl (CDC), because of the larger total number of events. For thisevaluation, the absolute numbers of infections and the actual patientpopulation were used to calculate the rate of each infection for eachmonth of the evaluation interval. The rates were reported in the unit ofevents per 1000 patient days. These monthly rates were averaged for theyear before application of the coating and the year after application,and compared.

The results are shown in Table 4, below, along with the results of atwo-tailed homoscedastic t-test. The decline in total of all infectionrates was statistically significant. Six of the seven infectioncategories that were monitored showed a decline in their average rates.However, not all infection categories were equally affected. Also,because the statistical test did not presume the direction of changethat might occur, the p-values were suggestive but not conclusive thatthe observed results did not occur by chance.

TABLE 4 12 months 12 months p Type of Infection before after valueGastrointestinal 0.358 0.333 0.858 Skin and Soft Tissue 1.017 0.7670.192 Bloodstream 0.033 0.017 0.557 Eye, Ear, Nose, 0.708 0.367 0.108Throat, or Mouth Urinary Tract 1.683 1.025 0.079 Upper Respiratory 0.2170.050 0.219 Lower Respiratory 0.533 0.648 0.536 TOTAL 4.567 3.225 0.016

To strengthen the statistical analysis, additional data was included ina subsequent analysis, and is shown in Table 5 below, along with theresults of a two-tailed homoscedastic t-test. As before, results for thegrouped infections of all types were statistically significantlydifferent. Six of the seven individual infection categories that weremonitored showed a decline in the average rate of occurance. However,the one infection category that showed an increase changed from lowerrespiratory to blood stream. It is likely that such shifts are a resultof the relatively low number of events overall, and that larger studiesare needed to define the full range of benefit. Nevertheless, five ofthe seven categories showed a decline in both analyses. This analysisalso strengthened the statistical evidence for a non-chance reduction ineye, ear, nose throat or mouth infection (EENT), urinary tractinfections (UTI), and upper respiratory infections (URI), with both EENTand UTI achieving formal statistical significance (p<0.05).

TABLE 5 12 months 17 months p Type of Infection before after valueGastrointestinal 0.358 0.300 0.626 Skin and Soft Tissue 1.017 0.9110.538 Bloodstream 0.033 0.044 0.764 Eye, Ear, Nose, 0.708 0.350 0.043Throat, or Mouth Urinary Tract 1.683 0.978 0.027 Upper Respiratory 0.2170.058 0.158 Lower Respiratory 0.533 0.499 0.836 TOTAL 4.567 3.172 0.004

It is important to note that the construction and arrangement of themethods and steps shown in the exemplary embodiments is illustrativeonly. Although only a few embodiments of the present disclosure havebeen described in detail, those skilled in the art will readilyappreciate that many modifications are possible without materiallydeparting from the novel teachings and advantages of the subject matterrecited in the claims. Accordingly, all such modifications are intendedto be included within the scope of the present disclosure as defined inthe appended claims. The order or sequence of any process or methodsteps may be varied or re-sequenced according to alternativeembodiments. Other substitution, modification, changes and omissions maybe made in the design, operating conditions and arrangement of theembodiments without departing from the spirit of the present disclosureas expressed in the appended claims.

All publications, patents and patent applications cited in thisspecification are herein incorporated by reference, and for any and allpurposes, as if each individual publication, patent or patentapplication were specifically and individually indicated to beincorporated by reference. In this case of inconsistencies, the presentdisclosure will prevail.

We claim:
 1. A method of reducing the incidence of healthcare-associatedinfections in a healthcare facility comprising treating at least oneinanimate surface of the healthcare facility structure, or at least oneobject therein, or a combination thereof, with a photocatalyticcomposition comprising titanium dioxide (TiO₂) doped with zinc and atleast one other doping agent.
 2. The method of claim 1, wherein thehealthcare-associated infection is selected from the group consisting ofbone infection, joint infection, bloodstream infection, central nervoussystem infection, cardiovascular system infection, pneumonia,reproductive tract infection, surgical site infection, gastrointestinalinfection, lower respiratory infection, upper respiratory infection,skin or soft tissue infection, bloodstream infection, eye infection, earinfection, nose infection, throat infection, mouth infection, andurinary tract infection.
 3. The method of claim 1, wherein thephotocatalytic composition is applied at a rate of from about 500 ft²per liter to about 1500 ft² per liter.
 4. The method of claim 3, whereinthe photocatalytic composition is applied by spraying, atomizing,coating, immersion, or dipping.
 5. The method of claim 1, wherein theincidence of healthcare-associated infections is reduced by at least 20%over a twelve month period after one treatment of the inanimate surfacesof the healthcare facility structure, at least one object therein, or acombination thereof.
 6. The method of claim 1, wherein the incidence ofhealthcare-associated infections is reduced by at least 30% over atwelve month period after one treatment of the inanimate surfaces of thehealthcare facility structure, or at least one object therein, or acombination thereof.
 7. The method of claim 1, wherein the step oftreating inanimate surfaces of the healthcare facility structure, or atleast one object therein, or a combination thereof, prevents and reducesthe presence at least one infectious agent selected from the groupconsisting of species of Acinetobacter, adenovirus, Bacillus,Burkholderia, Bordetella, Brucella, caliciviruses, herpes includingzoster (chickenpox), Clostridium, corona viruses including SARS, MERS,and PEDV, Enterococcus, Escherichia, Hemophilus, hepatitis viruses A andB, influenza and parainfluenza viruses, Klebsiella, Listeria,Legionella, measles virus, mumps virus, Mycobacterium, Neisseria,norovirus, Pseudomonas, parvovirus, poliovirus, rhinovirus, respiratorysyncyticia virus, rotavirus, rubella, Salmonella, Streptococcus,Staphylococcus, Vibrio, MRSA (methicillin-resistant Staphylococcusaureus, VISA (vancomycin intermediate Staphylococcus aureus), MRE(multiply resistant enterococci), and VRE (vancomycin-resistantenterococci)).
 8. The method of claim 1, wherein the at least oneinanimate surface includes walls, fixtures, floors, and ceilings ofhallways, offices, bathrooms, elevators, stairwells,kitchens/cafeterias, common areas, nurses' stations, and doctors'stations.
 9. The method of claim 1, wherein the at least one object isselected from the group consisting of curtains, call buttons, computers,monitors, wall computer kiosks, blood pressure cuffs, wheelchairs,lifts, carts, and beds.
 10. The method of claim 1, wherein the at leastone other doping agent increases the absorbance of light across therange of about 200 nm to about 500 nm.
 11. The method of claim 1,wherein the absorbance of light of wavelengths longer than about 450 nmis less than 50% the absorbance of light of wavelengths shorter thanabout
 350. 12. The method of claim 1, wherein the at least one otherdoping agent is selected from the group consisting of Ag, Si, C, S, Fe,Mo, Ru, Cu, Os, Re, Rh, Sn, Pt, Li, Na, and K.
 13. The method of claim1, wherein the titanium dioxide nanoparticles have an average particlesize of from about 2 nm to about 20 nm.
 14. The method of claim 1,wherein the at least one other doping agent is silicon.
 15. The methodof claim 1, wherein the at least one other doping agent is silicondioxide.
 16. The method of claim 15, the photocatalytic compositionhaving a ratio of titanium dioxide to silicon dioxide of from about 3 toabout
 20. 17. The method of claim 15, the photocatalytic compositionhaving a ratio of titanium dioxide to zinc from about 5 to about 150 anda ratio of titanium dioxide to silicon dioxide from about 1 to about500.
 18. The method of claim 1, wherein the photocatalytic compositionconsists essentially of: (A) about 5000 to about 10000 ppm of titaniumdioxide, (B) about 50 to about 150 ppm of zinc, and (C) about 300 toabout 1000 ppm of silicon dioxide.
 19. A method for preventing orreducing the number of infections in a human or animal populationcomprising treating inanimate surfaces of a structure occupied by thepopulation, or at least one inanimate object present therein, or acombination thereof, with a photocatalytic composition comprisingtitanium dioxide (TiO₂) doped with zinc and at least one other dopingagent.
 20. The method of claim 19, wherein the structure occupied by thepopulation is selected from the group consisting of an agriculturalfacility, food-processing facility, catering facility, restaurants,hotel, motel, and childcare facility.